Hedyotis diffusa willd-scutellaria barbata herbal Pair ameliorates colitis-associated colorectal cancer progression by modulating the gut microbiota and the PPARγ/NF-κB pathway.

Abstract

BACKGROUND: Hedyotis diffusa Willd. (HD)-Scutellaria barbata (SB) is one of the most commonly used herbal pairs in traditional Chinese medicine for cancer treatment, exhibiting notable antitumor and anti-inflammatory effects. This study aimed to investigate the effects and potential mechanism of HD-SB against colitis-associated colorectal cancer (CAC). METHODS: Herbal pairs for colorectal cancer treatment were analyzed through data mining of 233 traditional Chinese formulas. The chemical components of HD, SB, and various HD-SB ratios were determined by UPLC-Q-TOF/MS. To investigate the anti-CAC effect and underlying mechanisms of HD-SB, we employed network pharmacology, an AOM/DSS-induced CAC mouse model, 16S rRNA sequencing technology, untargeted metabolomics, and several biological methods. RESULTS: HD-SB emerged as the most frequently used herbal pair for colorectal cancer treatment among the 233 traditional formulas. Network pharmacology analysis indicate that HD-SB influences inflammation and immune-related pathways in CAC, notably the IL-17 signaling pathway, TNF signaling pathway, and NF-κB signaling pathway. HD-SB significantly inhibited CAC formation in the AOM/DSS induced mouse model. HD-SB also modulated gut microbiota composition and altered metabolites, including increased butyrate and deoxycholic acid levels. Additionally, HD-SB reduced intestinal inflammation through the PPARγ/NF-κB pathway and improved intestinal barrier function by upregulating claudin-1 and downregulating vimentin in the colon tissue of CAC mice. Fecal extract from HD-SB-treated mice showed a more pronounced inhibitory effect on AOM/DSS-induced tumorigenesis in pseudo germ-free mice compared to HD-SB treatment. CONCLUSION: HD-SB significantly inhibits CAC progression by modulating gut microbiota and the PPARγ/NF-κB signaling pathway.